Kaitocephalin Antagonism of Glutamate Receptors Expressed in Xenopus Oocytes AgenorLimon, † JorgeM.Reyes-Ruiz, † RishiG.Vaswani, ‡ A.RichardChamberlin, ‡,§

Kaitocephalin is the first discovered natural toxin with protective properties against excitotoxic death of cultured neurons induced by N-methyl-D-aspartate (NMDA) or R-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainic acid (kainate, KA) receptors. Nevertheless, the effects of kaitocephalin on the function of these receptors were unknown. In this work, we report some pharmacologicalpropertiesofsynthetic(-)-kaitocephalin on rat brain glutamate receptors expressed in Xenopus laevis oocytes and on the homomeric AMPA-type GluR3 and KA-type GluR6 receptors. Kaitocephalin was found to be a more potent antagonist of NMDA receptors (IC50 =7 5( 9 nM) than of AMPA receptors from cerebral cortex (IC50 =2 42( 37 nM) and from homomeric GluR3 subunits (IC50 =5 02( 55 nM). Moreover, kaitocephalin is a weak antagonist of the KA-type receptorGluR6(IC50 ∼100 μM) and of metabotropic (IC50 > 100 μM) glutamate receptors expressed by rat brain mRNA.